1. Field of the Invention
The present invention relates to probe sensing and, more specifically, to a system for controlling spacing in a probe sensor system with a high level of precision.
2. Description of the Prior Art
Conventional atomic force microscope (AFM) and its variations have been used to probe a wide range of physical and biological processes, including mechanical properties of single molecules, electric and magnetic fields of single atoms and electrons. Moreover, cantilever based structures inspired by the AFM have been a significant driver for nanotechnology resulting in chemical sensor arrays, various forms of lithography tools with high resolution, and terabit level data storage systems. Despite the current rate of success, the AFM needs to be improved in terms of speed, sensitivity, and an ability to generate quantitative data on the chemical and mechanical properties of the sample. For example, when measuring molecular dynamics at room temperature, the molecular forces need to be measured in a time scale that is less than the time of the thermal fluctuations to break the bonds. This requires a high speed system with sub-nanonewton and sub-nanometer sensitivity.
Current cantilever-based structures for AFM probes and their respective actuation methodologies lack speed and sensitivity and have hindered progress in the aforementioned areas. Imaging systems based on small cantilevers have been developed to increase the speed of AFMs, but this approach has not yet found wide use due to demanding constraints on optical detection and bulky actuators. Several methods have been developed for quantitative elasticity measurements, but the trade-off between force resolution, measurement speed, and cantilever stiffness has been problematic especially for samples with high compliance and high adhesion. Cantilever deflection signals measured during tapping mode imaging have been inverted to obtain elasticity information with smaller impact forces, but complicated dynamic response of the cantilever increases the noise level and prevents calculation of the interaction forces. Arrays of AFM cantilevers with integrated piezoelectric actuators have been developed for parallel lithography, but low cantilever speed and complex fabrication methods have limited their use.
Most of the scanning probe microscopy techniques, including tapping mode imaging and force spectroscopy, rely on measurement of the deflection of a micro-cantilever with a sharp tip. Therefore, the resulting force data depend on the dynamic properties of the cantilever, which shapes the frequency response. This can be quite limiting, as mechanical structures like cantilevers are resonant vibrating structures and they provide information mostly only around these resonances. For example, in tapping mode imaging it is nearly impossible to recover all the information about the tip-sample interaction force, since the transient force applied at each tap cannot be observed as a clean time signal.
Moreover, conventional methods of imaging with scanning probes can be time consuming while others are often destructive because they require static tip-sample contact. Dynamic operation of AFM, such as the tapping-mode, eliminates shear forces during the scan. However, the only free variable in this mode, the phase, is related to the energy dissipation and it is difficult to interpret. Further, the inverse problem of gathering the time-domain interaction forces from the tapping signal is not easily solvable due to complex dynamics of the AFM cantilever. Harmonic imaging is useful to analyze the sample elastic properties, but this method recovers only a small part of the tip-sample interaction force frequency spectrum.
Applications of atomic force microscopy (AFM) in life sciences have been increasing in both variety and significance. In addition to high resolution imaging of cells, DNA and other biological structures, AFM enables single-molecule mechanics studies characterizing both intra-molecular and intermolecular forces. Studying biological samples in aqueous environments, which can be corrosive and electrically conducting, imposes challenging electrical isolation requirements. This is especially important for AFM cantilevers or cantilever arrays with integrated piezoelectric detectors or piezoelectric actuators. To collect statistically significant data even on a single type of molecule, measurements need to be repeated many times, which requires durable sensors. To implement single-molecule experiments to protein chips for applications such as drug discovery and screening, the throughput needs to be significantly improved. This can be achieved by development of systems that can perform parallel single-molecule measurements on many different molecular pairs. Some parallel techniques have been demonstrated for bond rupture frequency measurements where a molecule of known mechanical properties is used as a force gauge. However, many other single-molecule experiments, such as those that measure bond lifetime at a clamped force, require applying controlled forces on molecules and measuring these forces with pico-Newton resolution. Therefore, both parallel actuation and parallel force sensing are required for parallel single-molecule mechanics experiments. AFM cantilever arrays with integrated piezoelectric actuators and either optical or piezo-resistive sensing have demonstrated this capability. These devices, which are used mainly for fast imaging so far, require complex fabrication processes and may be difficult to isolate electrically for operation in liquid environments.
Recently, membrane-based probe structures with electrostatic actuation and integrated diffraction-based optical interferometric displacement detection have been introduced for SPM applications. Initial implementation of these force sensing integrated readout and active tip (FIRAT) devices used aluminum membranes over an unsealed air cavity and hence was not suitable for operation in immersion. A version of these surface micromachined structures suitable for operation in biologically relevant, electrically conductive buffer solutions has already been realized for medical ultrasonic imaging applications. These capacitive micromachined ultrasonic transducers (CMUT) use a dielectric material such as silicon nitride as the structural membrane, and a metal actuation electrode buried in the dielectric membrane which is electrically isolated from the immersion medium. The cavity between the membrane and the bottom electrode is sealed under low pressure to prevent liquid leakage.
Thus, there is a need to overcome these and other problems of the prior art associated with probe microscopy.